We propose to build an advanced positron emission tomography (PET) system dedicated to breast cancer imaging. The system uses a novel position sensitive photon detector concept that has been developed under grant R21 CA098691 that we propose to translate into the clinic. This new sensor will help to push the performance limits of PET for cancer imaging. The design uses scintillation crystals coupled in an innovative manner to new, highly compact semiconductor photodetector arrays. This development allows us to achieve 1 mm spatial resolution with direct photon interaction depth measurement, high 511 keV photon detection efficiency, and a scintillation detector configuration that promotes >95% scintillation light collection efficiency for exceptional energy and coincident time resolution. Although this new photon sensor concept could in principle be utilized in any high resolution PET cancer imaging application, we are focusing on breast cancer because there is particular potential for high impact. PET has shown promise for breast cancer imaging, but has not been incorporated into standard practice due to inadequate breast cancer specificity and sensitivity, relatively long scan times, and high cost. If successful, our developments will have impact on increasing the role of PET in breast cancer management by addressing all of these issues. The proposed system will have 1 mm reconstructed spatial resolution in order to better visualize <2.5 mm structures of high focal uptake as indication of early breast cancer. This camera will use 2 cm thick, closely packed crystals, and close proximity breast imaging for up to 15% coincidence efficiency to help realize the desired spatial resolution proposed and rapidly (in 10 seconds) generate images. PET breast imaging poses particular challenges due to background activity in the thorax producing high random and Compton scatter coincident photon rates that result in lower lesion to background contrast. The excellent energy and temporal resolutions and flexible orientation achieved with the new design will help to reduce background photon scatter and random effects on lesion contrast. This system will also help breast cancer researchers to evaluate more specific breast cancer tracers and monitor potential treatments. For this five-year project we will integrate the novel detector modules into a gantry, develop a data acquisition system, implement data correction, calibration, and image reconstruction algorithms, and test the system with point source measurements.